Spatial and temporal distribution of laminins in permanent focal ischemic brain damage of the adult rat.

Laminins are extracellular matrix glycoproteins with multiple functions in the central nervous system, including maintenance of the blood-brain barrier. Because ischemic brain damage results in rapid degradation of extracellular matrix, we used immunocytochemistry on rat central nervous system after permanent focal ischemia to identify laminins involved in pathophysiology of stroke. At 24 hr after stroke, laminin-1 is transiently expressed by neurons inside the ischemic core, but from 2-3 days to 28 days it is expressed only in basement membrane structures.

Selective overexpression of gamma1 laminin in astrocytes in amyotrophic lateral sclerosis indicates an involvement in ALS pathology.

Our earlier studies indicate that the KDI tripeptide of gamma1 laminin reverts paralysis and protects adult rat CNS from excitotoxicity of glutamate and from oxidative stress. Here we show that gamma1 laminin is selectively overexpressed in reactive astrocytes of the amyotrophic lateral sclerosis (ALS) spinal cord, with both gray and white matter astrocytes overexpressing gamma1 laminin. Intensely gamma1 laminin-positive, aggressive-looking reactive astrocytes of the lateral columns of both cervical and thoracic spinal cord surround the lateral ventral horns and roots and extend into the area of the lateral corticospinal tract.

KDI tripeptide of gamma1 laminin protects rat dopaminergic neurons from 6-OHDA induced toxicity.

Our previous studies indicate that the KDI (Lys-Asp-Ile) tripeptide of gamma1 laminin protects central neurons from mechanical trauma and excitotoxicity. At least part of the neuroprotective effect of the KDI tripeptide may be mediated by its inhibitory function on ionotropic glutamate receptors. We studied the protective effect of the KDI tripeptide against 6-hydroxy-dopamine (6-OHDA) induced neurotoxicity in a rat experimental model of Parkinson's disease (PD).

The neuroprotective KDI domain of gamma 1-laminin is a universal and potent inhibitor of ionotropic glutamate receptors.

Previous work from this laboratory indicates that the KDI (Lys-Asp-Ile) domain of gamma 1-laminin promotes functional regeneration of adult rat spinal cord injuries and protects adult rat hippocampal neurons against massive neuronal death induced by intracerebral injection of the glutamate analogue kainic acid. In the present study, we used patch clamp recordings on cultured human embryonic neocortical neurons and HEK 293 cells expressing recombinant glutamate receptor subunits to study a putative interaction of the KDI with the glutamate system. We show that the KDI domain of gamma 1-laminin is a universal and potent inhibitor of AMPA, kainate, and NMDA subclasses of glutamate receptors, with a noncompetitive action on the AMPA receptor channel activity.

Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of gamma1 laminin.

Regeneration in the central nervous system (CNS) of adult mammals is hampered by formation of a glial scar and by proteins released from the myelin sheaths of injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile) domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory signals and promotes survival and neurite outgrowth of cultured human spinal cord neurons. We show that after complete transection of the adult rat spinal cord, animals receiving onsite infusion of the KDI domain via osmotic mini-pumps recover and are able to sustain their body weights and walk with their hindlimbs.